Skip to main content

Advertisement

Log in

LINC00667 Promotes Progression of Esophageal Cancer Cells by Regulating miR-200b-3p/SLC2A3 Axis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Recently, more and more evidence indicated that the long non-coding RNA was strictly related to the occurrence and progression of human cancers, including esophageal cancer (EC). We observed that LINC00667 was increased in EC, but the function of LINC00667 was unclear. Therefore, the function and potential molecular mechanism of LINC00667 in the progression of EC need to be further studied.

Methods

Quantitative real-time PCR was used to investigate the levels of LINC00667, miR-200b-3p, and SLC2A3. The levels of protein involved in cell cycle, cell apoptosis, epithelial–mesenchymal transition, as well as SLC2A3 were quantitatived by western blot. The role of LINC00667 in the proliferative, migratory and invasive capabilities of EC cells were measured by cell counting kit-8 assay, EdU assay, flow cytometry assay, wound healing assay and transwell assay, respectively. Interaction between LINC00667 and miR-200b-3p or miR-200b-3p and SLC2A3 were confirmed using a luciferase reporter assay.

Results

In this work, we found that LINC00667 expression was up-regulated in EC cell lines, and LINC00667 knockdown inhibited cell proliferation, migration, and invasion in EC cells. In addition, it showed that LINC00667 functioned as competitive endogenous RNA for miR-200b-3p by the DIANA-LncBase database. Moreover, we used targetscan online software to predict SLC2A3 as a target gene of miR-200b-3p. Subsequently, rescue experiments confirmed that knocking out SLC2A3 could reverse the inhibitory effect of miR-200b-3p on EC cells transfected with sh-LINC00667.

Conclusion

Herein, we revealed the novel mechanism of LINC00667 on regulating metastasis-related gene by sponge regulatory axis during EC metastasis. Our results demonstrated that LINC00667 plays a critical role in metastatic EC by mediating sponge regulatory axis miR-200b-3p/SLC2A3. To explore function of LINC00667/miR-200b-3p/SLC2A3 axis may provide an informative biomarker of malignancy and a highly selective anti-EC therapeutic target.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The raw data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study.

Abbreviations

EC:

Esophageal cancer

EMT:

Epithelial–mesenchymal transition

CCK-8:

Cell counting kit-8

ceRNA:

Competitive endogenous RNA

GLUT:

Glucose transporter

References

  1. Alaei S, Sadeghi B, Najafi A, Masoudi-Nejad A. LncRNA and mRNA integration network reconstruction reveals novel key regulators in esophageal squamous-cell carcinoma. Genomics. 2019;111:76–89. https://doi.org/10.1016/j.ygeno.2018.01.003.

    Article  CAS  PubMed  Google Scholar 

  2. Ancey PB, Contat C, Meylan E. Glucose transporters in cancer—from tumor cells to the tumor microenvironment. FEBS J. 2018;285:2926–2943. https://doi.org/10.1111/febs.14577.

    Article  CAS  PubMed  Google Scholar 

  3. Chen D, Wang H, Chen J et al. MicroRNA-129-5p regulates glycolysis and cell proliferation by targeting the glucose transporter SLC2A3 in gastric cancer cells. Front Pharmacol. 2018;9:502. https://doi.org/10.3389/fphar.2018.00502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chen J, Kwong DL, Cao T et al. Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics. Dis Esophagus. 2015;28:84–89. https://doi.org/10.1111/dote.12088.

    Article  CAS  PubMed  Google Scholar 

  5. Chen M-J, Deng J, Chen C, Hu W, Yuan Y-C, Xia Z-K. LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis. Int J Biochem Cell Biol. 2019;113:27–36. https://doi.org/10.1016/j.biocel.2019.05.011.

    Article  CAS  PubMed  Google Scholar 

  6. Chu J, Li H, Xing Y et al. LncRNA MNX1-AS1 promotes progression of esophageal squamous cell carcinoma by regulating miR-34a/SIRT1 axis. Biomed Pharmacother. 2019;116:109029. https://doi.org/10.1016/j.biopha.2019.109029.

    Article  CAS  PubMed  Google Scholar 

  7. Codipilly DC, Qin Y, Dawsey SM et al. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc. 2018;88:413–426. https://doi.org/10.1016/j.gie.2018.04.2352.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Deng D, Sun P, Yan C et al. Molecular basis of ligand recognition and transport by glucose transporters. Nature. 2015;526:391–396. https://doi.org/10.1038/nature14655.

    Article  CAS  PubMed  Google Scholar 

  9. Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa Á. Esophageal cancer: risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21:7933–7943. https://doi.org/10.3748/wjg.v21.i26.7933.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Grote P, Boon RA. LncRNAs coming of age. Circ Res. 2018;123:535–537. https://doi.org/10.1161/CIRCRESAHA.118.313447.

    Article  CAS  PubMed  Google Scholar 

  11. Huang T-X, Fu L. The immune landscape of esophageal cancer. Cancer Commun. 2019;39:79. https://doi.org/10.1186/s40880-019-0427-z.

    Article  Google Scholar 

  12. Kato H, Nakajima M. Treatments for esophageal cancer: a review. Gener Thorac Cardiovasc Surg. 2013;61:330–335. https://doi.org/10.1007/s11748-013-0246-0.

    Article  Google Scholar 

  13. Kennedy BM, Harris RE. Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer. Inflammopharmacology. 2018. https://doi.org/10.1007/s10787-018-0489-6.

    Article  PubMed  Google Scholar 

  14. Koutsioumpa M, Hatziapostolou M, Polytarchou C et al. Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming. Gut. 2019;68:1271–1286. https://doi.org/10.1136/gutjnl-2017-315690.

    Article  CAS  PubMed  Google Scholar 

  15. Liu P, Chen S, Huang Y et al. LINC00667 promotes Wilms’ tumor metastasis and stemness by sponging miR-200b/c/429 family to regulate IKK-β. Cell Biol Int. 2020;44:1382–1393. https://doi.org/10.1002/cbin.11334.

    Article  CAS  PubMed  Google Scholar 

  16. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141:1202–1207. https://doi.org/10.1016/j.jaci.2017.08.034.

    Article  CAS  PubMed  Google Scholar 

  17. Lv Z, Wei J, You W et al. Disruption of the c-Myc/miR-200b-3p/PRDX2 regulatory loop enhances tumor metastasis and chemotherapeutic resistance in colorectal cancer. J Transl Med. 2017;15:257. https://doi.org/10.1186/s12967-017-1357-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ma H-W, Xi D-Y, Ma J-Z et al. Long noncoding RNA AFAP1-AS1 promotes cell proliferation and metastasis via the miR-155-5p/FGF7 axis and predicts poor prognosis in gastric cancer. Dis Mark. 2020;2020:8140989. https://doi.org/10.1155/2020/8140989.

    Article  CAS  Google Scholar 

  19. Ma J, Xiao Y, Tian B et al. Long noncoding RNA lnc-ABCA12-3 promotes cell migration, invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma. J Cell Biochem. 2020;121:1374–1387. https://doi.org/10.1002/jcb.29373.

    Article  CAS  PubMed  Google Scholar 

  20. Mao Y, Fu Z, Zhang Y et al. A seven-lncRNA signature predicts overall survival in esophageal squamous cell carcinoma. Sci Rep. 2018;8:8823. https://doi.org/10.1038/s41598-018-27307-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Militello G, Weirick T, John D, Döring C, Dimmeler S, Uchida S. Screening and validation of lncRNAs and circRNAs as miRNA sponges. Brief Bioinform. 2017;18:780–788. https://doi.org/10.1093/bib/bbw053.

    Article  CAS  PubMed  Google Scholar 

  22. Moghbeli M, Mosannen Mozaffari H, Memar B et al. Role of MAML1 in targeted therapy against the esophageal cancer stem cells. J Transl Med. 2019;17:126. https://doi.org/10.1186/s12967-019-1876-5.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Peng L, Cheng S, Lin Y et al. CCGD-ESCC: a comprehensive database for genetic variants associated with esophageal squamous cell carcinoma in Chinese population. Genomics Proteom Bioinform. 2018;16:262–268. https://doi.org/10.1016/j.gpb.2018.03.005.

    Article  Google Scholar 

  24. Peng W, Si S, Zhang Q et al. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015;34:79. https://doi.org/10.1186/s13046-015-0197-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Short MW, Burgers KG, Fry VT. Esophageal cancer. Am Fam Phys. 2017;95:22–28.

    Google Scholar 

  26. Smyth EC, Lagergren J, Fitzgerald RC et al. Oesophageal cancer. Nat Rev Dis Primers. 2017;3:17048. https://doi.org/10.1038/nrdp.2017.48.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tong YS, Wang XW, Zhou XL et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3. https://doi.org/10.1186/1476-4598-14-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tsui NB, Ng EK, Lo YM. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin Chem. 2002;48:1647–1653.

    Article  CAS  Google Scholar 

  29. Wang P-S, Chou C-H, Lin C-H et al. A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer. Oncogene. 2018;37:4662–4678. https://doi.org/10.1038/s41388-018-0293-1.

    Article  CAS  PubMed  Google Scholar 

  30. Watanabe M, Otake R, Kozuki R et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today. 2020;50:12–20. https://doi.org/10.1007/s00595-019-01878-7.

    Article  PubMed  Google Scholar 

  31. Xu LJ, Yu XJ, Wei B et al. LncRNA SNHG7 promotes the proliferation of esophageal cancer cells and inhibits its apoptosis. Eur Rev Med Pharmacol Sci. 2018;22:2653–2661. https://doi.org/10.26355/eurrev_201805_14961.

    Article  PubMed  Google Scholar 

  32. Zhang F, Zhang M. Oleuropein inhibits esophageal cancer through hypoxic suppression of BTG3 mRNA. Food Funct. 2019;10:978–985. https://doi.org/10.1039/c8fo02223b.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang H, Hua Y, Jiang Z et al. Cancer-associated fibroblast-promoted LncRNA confers radioresistance by regulating DNA damage response in esophageal squamous cell carcinoma. Clin Cancer Res. 2019;25:1989–2000. https://doi.org/10.1158/1078-0432.CCR-18-0773.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang L, Chen J, Wang L et al. Linc-PINT acted as a tumor suppressor by sponging miR-543 and miR-576-5p in esophageal cancer. J Cell Biochem. 2019;120:19345–19357. https://doi.org/10.1002/jcb.28699.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang Z-W, Chen J-J, Xia S-H et al. Long intergenic non-protein coding RNA 319 aggravates lung adenocarcinoma carcinogenesis by modulating miR-450b-5p/EZH2. Gene. 2018;650:60–67. https://doi.org/10.1016/j.gene.2018.01.096.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We deeply appreciate the support by all participants.

Funding

No funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jindun Pan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, J., Zang, Y. LINC00667 Promotes Progression of Esophageal Cancer Cells by Regulating miR-200b-3p/SLC2A3 Axis. Dig Dis Sci 67, 2936–2947 (2022). https://doi.org/10.1007/s10620-021-07145-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-021-07145-5

Keywords

Navigation